Hyaluronic acid, or HA, is a natural glycosaminoglycan that is very abundant in all mesodermal tissues, in the vitreous humour and in Wharton's jelly in the umbilical cord. It is present in the intercellular matrix of tissues, in the different tissues of all animal species, and has a significant role in the skin structure, being responsible for the elasticity thereof. It has the capacity to retain a large amount of water around it, thereby providing volume to the tissues.
Its structure consists of alternating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine bound by β-1-3 and β-1-4 glycosidic bonds. Unlike other polysaccharides, HA does not have a defined shape in space, but spreads in a random manner and tends to occupy a very large volume due to the electrostatic repulsion of the carboxyl groups of glucuronic acid. At the same time, it forms meshes that retain a large amount of water.
HA has a decisive role as a connective element in tissues. The skin contains close to 56% of the HA present in the body. The body dermis has a lattice network of collagen fibres inside an interstitial substance that is largely composed of HA. This acid's elastic properties provide resistance against compression, and this is how the skin protects the underlying structures against external aggressions, whereas the non-Newtonian properties of HA allow the collagen fibres to easily move through the interstitial substance. This lubrication process by means of HA allows the skin to adapt to the changes in shape and volume that take place when the bones and ligaments move.
As we age, the quantity of HA in the skin decreases, since the skin cells progressively lose their production capacity. Furthermore, the molecular weight of HA decreases with age, such that it does not preserve water as it previously did. This decrease in volume is what causes wrinkles. It is estimated that, at the age of 40, the amount of HA in the skin has decreased by half. After the age of 60, only 10% remains.
HA has been used in cosmetics since 1996; it may be of animal origin (from hens' combs and fish's eyeballs) or of biological origin (bacterial culture extracts). HA is responsible for the elasticity of the skin. It is a great remedy against wrinkles, since it increases the volume in skin folds, grooves and depressions. The periodical application thereof causes the regeneration of the skin's own collagen. The advantage of this product is that it is a substance that is compatible with all tissues; therefore, it does not require any type of cutaneous test, as is the case with collagen.
Cosmetic treatments based on HA are well-known in the state of the art. However, the cosmetic application of HA entails the loss of the conformation of HA and, consequently, a decrease in stability and water-retaining capacity.
Therefore, the state of the art still needs to provide new HA compounds that improve the lifetime and stability of HA in order that it may be used in cosmetic treatments.
In this regard, the inventors have been surprised to discover that conjugating HA oligomers with the surface of a metal nanoparticle through a linker improves the properties of physical structure, stability and durability, and, in general, transdermal penetration properties. Therefore, the cosmetic application of this conjugate provides an effective, lasting wrinkle-filler effect on the skin, which may replace other less effective treatments.